Background

Gestational diabetes mellitus (GDM), defined as any degree of glucose intolerance with onset or first recognition during pregnancy, affects 2-10% pregnancies in the United States.
[1, 2] Women with gestational diabetes have a 35-60% chance of developing diabetes mellitus over 10-20 years after pregnancy.
[1]

The Western diet of high fat, high carbohydrate, and high sodium foods is a significant contributor to excessive weight gain during pregnancy and, thus, a risk factor for developing diabetes. Other risk factors, which should be assessed at the first prenatal visit, include obesity, age greater than 25 years, prior history of gestational diabetes, first-degree relative with diabetes, history of poor obstetrical outcome, and certain ethnic groups.
[6]

Women with underlying insulin resistance are at risk for developing GDM. This progression to GDM is thought to be due to physiologic changes of late pregnancy. In pregnancy, human placental lactogen, which is structurally similar to growth hormone, and tumor-necrosis factor-alpha induce changes in the insulin receptor and in post-receptor signaling. Changes in the beta-subunit of the insulin receptor, decreased phosphorylation of tyrosine kinase on the insulin receptor, and alterations in insulin receptor substrate-1 (IRS-1) and the intracytoplasmic phosphatidylinositol 3-kinase (PI3K) appear to be involved in reducing glucose uptake in skeletal muscle tissue.
[7]

The Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) was a large randomized control trial that investigated the role of screening and treatment of gestational diabetes in reducing perinatal complications, improving maternal outcomes, and affecting quality of life.
[8] This trial of 1000 participants showed a composite reduction in serious perinatal morbidity and mortality (death, shoulder dystocia, bone fracture, and nerve palsy) in the intervention group compared to the conventional group. Also, a decrease in prevalence in macrosomia in the intervention group infants and reduced rate of gestational hypertension in the intervention group was found.
[8]

Another large, multicenter randomized controlled trial conducted in the United States recruited women with mild gestational diabetes mellitus. One group received treatment consisting of dietary changes, self-monitoring of blood glucose and insulin if needed and the other received the usual prenatal care. Outcomes with respect to perinatal and obstetrical outcomes were compared.
[9] This trial of 19,665 participants used slightly different parameters to diagnose gestational diabetes mellitus but had similar outcomes. There was a significant reduction in macrosomia with the treatment group as well as reduction in rates of Cesarean delivery, shoulder dystocia, preeclampsia or gestational hypertension and weight gain.

Finally, the HAPO trial (Hyperglycemia and Adverse Pregnancy Outcomes), which included over 23,000 pregnant women, sought to clarify risks of adverse outcomes associated with various degrees of maternal glucose intolerance less severe than overt diabetes mellitus.
[10] The study results showed positive linear correlations between increasing levels of fasting, 1-hour and 2-hour plasma glucose after oral glucose tolerance testing (OGTT), and macrosomia and cord-blood C-peptide levels above the 90th percentile. Weaker associations were noted between glucose levels and cesarean delivery and neonatal hypoglycemia. The secondary outcomes of premature delivery, shoulder dystocia, hyperbilirubinemia, and preeclampsia were also noted to increase in incidence with higher levels of post OGTT glucose levels.
[10]

The HAPO trial showed that maternal, fetal, and neonatal outcomes increased significantly with maternal hyperglycemia even at lower threshold ranges than prior diagnostic criteria for GDM. This prompted the International Association of Diabetes and Pregnancy study groups (IADPSG), whose committee consists of members from US and International diabetes organizations, including American Diabetes Association (ADA), and obstetrical organizations, to revise recommendations for diagnosing GDM. Whereas previously in the 2005 Fifth International Workshop-Conference on Gestational Diabetes Mellitus screening was based on risk stratification, now the IADPSG along with the ADA recommend that all women with no prior history of diabetes undergo 75-g Glucola oral glucose tolerance test (OGTT) at 24-28 weeks gestation.
[11, 12]

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Indications

All pregnant women need to be screened for gestational diabetes. The timing of the screening depends on risk factor assessment. Pregnant women with no known history of diabetes are screened at 24-28 weeks gestation. Women at high risk for GDM are screened at the first prenatal visit. A 75-g 2-hour OGTT is the test of choice in both groups.
[11]

The risk factors for GDM are as follows:

Increased weight (ie, BMI greater than or equal to 25)

Decreased physical activity

First degree relative with diabetes

Member of ethnic group with high prevalence of diabetes (African American, Latino, Native American, Asian American, Pacific Islander)

The 75-g Glucola OGTT is best performed after an overnight fast; the diagnosis is made if fasting plasma glucose is documented at 92mg/dL or higher, a 1-hr plasma glucose of 180 mg/dL or higher, or a 2-hr plasma glucose of 153 mg/dL or higher. The diagnosis of gestational diabetes is confirmed with a minimum of one abnormal value. The cut-offs were based on the prior HAPO study outcomes.
[13]

The standard criteria for the diagnosis of diabetes is as follows:

HbA1c of 6.5% or higher

Fasting plasma glucose of 126 mg/dL or higher or

2-h plasma glucose of 200 mg/dL or higher during an 75-g OGTT or

A symptomatic patient with random plasma glucose of 200 or higher (all plasma glucose values are recorded as mg/dL).

The pregnant women who meet the above criteria are considered to have overt type 2 diabetes mellitus.
[11]

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Contraindications

No known contraindications to gestational diabetes testing protocol, although some patients may experience nausea, gastric irritation, and delayed emptying from the Glucola.

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Technical Considerations

Two major changes from the previous diagnostic guidelines are lower diagnostic cut points for the fasting, 1-hour and 2-hour plasma glucose measurements and needing only one abnormal value to make the diagnosis versus 2 abnormal values in the previous guidelines. The implications of increased health care costs and a predictable increase in the diagnosis of GDM, possibly up to 18% of all pregnancies, have not been studied yet.
[13] Also, the intensity of monitoring and treating these women is not yet known in terms of maternal and neonatal outcomes.
[11, 13]

Comparatively, the American College of Obstetricians and Gynecologists (ACOG) has not adopted the IADPSG and ADA guidelines in gestational diabetes testing protocol.
[14] In the most recent committee opinion, September 2011, ACOG recommends screening for GDM at initial prenatal visit by history, risk factors or 50 gram/1-hour OGTT. The diagnosis of GDM continues to be based on the 100 gram/3-hour tolerance test using the Carpenter and Coustan cutoffs of fasting less than 95mg/dL, 1-hr less than 180 mg/dl, 2-hr less than 155 mg/dL, and 3-hr less than 140 mg/dL, with 2 or more abnormal values to confirm diagnosis.

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Outcomes

As stated above, diagnosis of GDM is made if any of the following plasma glucose values are exceeded after 75 grams Glucola is given:

Fasting of 92 mg/dL or higher (5.1 mmol/L)

1 hour of 180 mg/dL or higher (10 mmol/L)

2 hour of 153 mg/dL or higher (8.5 mmol/L)

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Epidemiology

New content

Gestational diabetes mellitus (GDM) is a severe and neglected threat to maternal and child health. Many women with GDM experience pregnancy-related complications including high blood pressure, large birth weight babies and obstructed labour. Approximately half of women with a history of GDM go on to develop type 2 diabetes within five to ten years after delivery. Every year, 2% to 10% of pregnancies in the United States are affected by gestational diabetes.
[15, 16]

The prevalence of high blood glucose (hyperglycaemia) in pregnancy increases rapidly with age and is highest in women over the age of 45. In 2017 there were an estimated 204 million women (20-79 years) living with diabetes. This number is projected to increase to 308 million by 2045. 1 in 3 women with diabetes were of reproductive age. 21.3 million or 16.2% of live births had some form of hyperglycaemia in pregnancy. An estimated 85.1% were due to gestational diabetes. 1 in 7 births was affected by gestational diabetes. The vast majority of cases of hyperglycaemia in pregnancy were in low- and middle-income countries, where access to maternal care is often limited.
[15]

American College of Obstetricians and Gynecologists. Screening and diagnosis of gestational diabetes mellitus. Committee Opinion No. 504. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2011. 118:751-3.